Monitoring, Audits, and InspectionOh my!

Rachel SheppardRegulatory Director, OCRSS

Types of Review• Routine monitoring• Quality assurance audit• IRB • Audit Services• Sponsor

• Routine investigation• For cause investigation

Key parties • PI• Data coordinator/study coordinator• Research nurse• Investigational pharmacist• IRB• Parts of Hospital• Contracts office

Monitoring• Planned review of documentation and data• ICF documentation• Screening documentation• Diagnostic test review documentation• Source documentation• Reporting of events to IRB/sponsor• IP inventory and dispensation

• Changes in monitoring• High turnover

Monitoring continued• Important relationship• Good monitor vs. bad monitor• Collaborative works best• Open items must be reviewed again• Documentation of all requests

IRB audit• Review of regulatory and clinical files• Different levels• Full board review• Cause and not for cause• Not for Cause triggered by• New investigator• Random

• For Cause triggered by• External governing agency audit• CAR document review• Excessive deviations

FDA Audit• Routine- verification of data quality, compliance and subject

protection• High enrollment• First in data• High profile study

• Directed – for cause• Patient complaint• Whistle blower• Offshoot of other investigation• Serious events

• Credentials and 482

Steps to prepare• Do not panic• Get all the information• Timeline• Scope• Type of audit

• Notify all parties• Designate contact for auditor• Assign duties to staff for audit• Arrange workspace and meeting space• Prepare staff for questions

Responding to questions• Understand question – ask for clarifications• Take your time answering (think first)• Answer only what is asked• Tell the truth• Do not argue and be positive• Tell the auditor/investigator if you do not know• Take notes on what was asked (after)

Documents• Regulatory files• CRFs and source documents• Ensure access to eCRFs• SOPs• IP accountability records• List of all projects PI has ongoing• Request medical records

Close out meeting• Discussion of findings• Notify investigator/auditors of any corrective actions taken• FDA 483• Clarify any discrepancies on 483• Involve university offices in any written responses

Best Practices• Document, document, document• Keep a binder of ICF copies• Consistency of documentation• Have and know SOPs• Have isolated workspace to limit access • Control copy access• Only supply requested information• Designate an escort/assistant• Be helpful

Best Practices• Don’t wait for an audit to have good records• Identify and report problems • CAP (correct and prevent)• Document correction methods• Evaluate that CAP works

Reference material• 21CFR50, 21CFR56, 21CFR312, ICH E:6• 21CFR: 312.68 Part 312 -- Investigational New Drug Application/Inspection of • investigator's records and reports• FDA: Bioresearch Monitoring: Clinical Investigators and Sponsor Investigators Guidance

for FDA staff• FDA: Bioresearch Monitoring: FDA/ORA Bioresearch Monitoring • FDA: Compliance Program Guidance Manual (CPGM) (Chapter 48)• FDA Guidance: Computerized Systems Used in Clinical Investigations• FDA Guidance: FDA Inspections of Clinical Investigators• FDA: Form 483 Frequently Asked Questions• Sheet: Guidance for IRBs, Clinical Investigators, and Sponsors: FDA • ICH: International Committee on Harmonization (ICH) E: 6 Good Clinical • FDA: Investigations Operations Manual• FDA Guidance: Investigator Responsibilities — Protecting the Rights, Safety, and • Welfare of Study Subjects• FDA Guidance: Part 11, Electronic Records, Electronic Signatures – Scope and • FDA: Preparing for a Clinical Investigator Inspection• FDA: Regulatory Procedures Manual (RPM)